Major Depressive Disorder
Conditions
Brief summary
The primary purpose of your participation in this study is to help answer the following research question, and not to provide you treatment for your condition. Whether duloxetine once daily orally is tolerated and safe, in children (aged 7 through 11 years) and adolescents (aged 12 through 17 years) with Major Depressive Disorder.
Interventions
DRUGduloxetine
20 - 120 milligrams (mg) every day, once-daily (QD), by mouth (PO) for 30 weeks; If patient is ≤40 kilograms (kg), initial dose is 20 mg, then titrated up. If patient is \>40 kg, initial dose is 30 mg, then titrated up.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male / Female outpatients 7 to 17 years of age diagnosed with Major Depressive Disorder (MDD). (Must have a Children's Depression Rating Scale-Revised \[CDRS-R\] with a total score greater than or equal to 40 at Visit 1, Visit 2, and Visit 3 and a Clinical Global Impressions of Severity \[CGI-Severity\] rating of greater than or equal to 4 at Visit 1, Visit 2, and Visit 3.) * Female patients must test negative on a pregnancy at visit 1.
Exclusion criteria
* Have a serious or unstable medical illness, psychological condition, clinically significant laboratory or electrocardiogram (ECG) result, hypersensitivity to duloxetine, or to its inactive ingredients, frequent or severe allergic reactions to multiple medications, uncontrolled narrow-angle glaucoma, acute liver injury (for example, hepatitis) or severe cirrhosis (Child-Pugh Class C) that in the opinion of the investigator would compromise participation in the study or be likely to lead to hospitalization during the course of the study. * Have a current or previous diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, anorexia, bulimia, obsessive compulsive disorder, pervasive development disorder or borderline personality disorder, as determined by the investigator. * Have a significant suicide attempt within 1 year of Visit 1 or have a score of 5 or greater on Item 13 (Suicidal Ideation) on the CDRS-R at Visit 1, Visit 2, or Visit 3, or are currently at risk of suicide in the opinion of the investigator. * Have a weight less than 20 kg at any Screening Phase visit. * Have previous exposure to duloxetine * Female patients who are either pregnant, nursing or have recently given birth.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Potentially Clinically Significant Electrocardiograms at Any Time in Period IV | Between 18 and 30 Weeks | Total number of patients with any abnormal post-baseline values, based on all values at scheduled and unscheduled visits. Criteria: High QRS Interval = ≥100 milliseconds (msec); High QTc Bazette's or Fredericia's correction - Female = ≥470 msec; High QTc Bazette's or Fredericia's correction - Male = ≥450 msec. |
| Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period IV | Between 18 and 30 Weeks | Total number of patients with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Criteria: High Diastolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Systolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Pulse = increase of at least 25 to a value of at least 110. |
| Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | Baseline to 18 Weeks | The results shown are for all laboratory analytes where PCS criteria were met, based on criteria used for adult studies. Criteria: High Alanine transaminase (\>165 Units/Liter \[U/L\]); High Creatine Phosphokinase (females: \>507 U/L; males:\>594 U/L); Low Glucose (\<2.498 millimoles/L); Low Hematocrit (females: \<0.32; males \<0.37); Low Hemoglobin (females \<5.896 millimoles/L \[mmol/L\] iron; males \<7.137 mmol/L iron); High Inorganic Phosphorus (\>1.776 millimoles/L); Low Leukocyte Count (\<2.8 X10\^9/L). |
| Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period IV | Between 18 and 30 Weeks | The results shown are for all laboratory analytes where PCS criteria were met, based on criteria used for adult studies. Criteria: High Alkaline Phosphatase (\>420 Units/Liter \[U/L\]); Low Hematocrit (females \<0.32; males \<0.37); High Inorganic Phosphorus (\>1.776 millimoles/L). |
| Number of Participants Meeting Criteria for Potentially Clinically Significant Electrocardiograms at Any Time in Period II/III | Baseline to 18 Weeks | Total number of patients with any abnormal post-baseline values, based on all values at scheduled and unscheduled visits. Criteria: High QRS Interval = ≥100 milliseconds (msec); High QTc Bazette's or Fredericia's correction - Female = ≥470 msec; High QTc Bazette's or Fredericia's correction - Male = ≥450 msec. |
| Number of Participants With Emergence of Suicidal Ideation During Period II/III | Baseline to 18 weeks | Emergence of Any Suicidal Ideation: Item 13 of Children's Depression Rating Scale-Revised (CDRS-R) has possible scores of 1 (no thoughts of suicide) to 7 (contemplation of suicide). Emergence of suicidal ideation was defined as an increase in severity of suicidal ideation for those patients who did not have suicidal ideation at baseline (Week 0). |
| Number of Participants With Emergence of Suicidal Ideation During Period IV | Week 0 and Between 18 and 30 Weeks | Emergence of Any Suicidal Ideation: Item 13 of Children's Depression Rating Scale-Revised (CDRS-R) has possible scores of 1 (no thoughts of suicide) to 7 (contemplation of suicide). Emergence of suicidal ideation was defined as an increase in severity of suicidal ideation for those patients who did not have suicidal ideation at baseline (Week 0). |
| Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period II/III | Baseline to 18 Weeks | The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline. |
| Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period IV | Between 18 and 30 Weeks | The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline. |
| Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period II/III | Baseline to 18 Weeks | Total number of patients with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Criteria: High Diastolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Systolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Pulse = increase of at least 25 to a value of at least 110. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose | Weeks 2, 4, 6, 8, 10, 14, 18 | Plasma samples were obtained at steady state, and approximately 95% of duloxetine concentrations were within the 24 hour dosing interval. |
| Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S) | Week 0 (Baseline), 18 Weeks, 30 Weeks | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Baseline is the same timepoint (Week 0) for both comparisons, but due to differences in number of patients in both periods (II/III vs IV), the baseline values may be slightly different. |
| Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | Week 0 (Baseline), 18 Weeks, 30 Weeks | Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression. Baseline is the same timepoint (Week 0) for both comparisons, but due to differences in number of patients in both periods (II/III vs IV), the baseline values may be slightly different. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Leading to Discontinuation | Week 0 (Baseline) to 30 Weeks | A listing of adverse events leading to discontinuation from the study. Abbreviation in data table: ADHD = Attention-Deficit/Hyperactivity Disorder. |
Countries
United States
Participant flow
Pre-assignment details
Period I was a 2-week Screening/Washout Phase. Period II was a 10-week Dose-Titrating with Pharmacokinetic Sampling Phase. Period III was an 8-week Safety and Tolerability Phase. Period IV was a 3-month Extended Safety and Tolerability Phase. Period V was a 2-week Taper Phase. Results presented are for combined Periods II/III and Period IV.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 20 - 120 milligrams (mg) every day, once-daily (QD), by mouth (PO) for 30 weeks; If patient is ≤40 kilograms (kg), initial dose is 20 mg, then titrated up. If patient is \>40 kg, initial dose is 30 mg, then titrated up. | 72 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Study Period II/III | Adverse Event | 3 |
| Study Period II/III | Lack of Efficacy | 2 |
| Study Period II/III | Lost to Follow-up | 3 |
| Study Period II/III | Parent/Caregiver Decision | 9 |
| Study Period II/III | Physician Decision | 3 |
| Study Period II/III | Protocol Violation | 3 |
| Study Period II/III | Withdrawal by Subject | 1 |
| Study Period IV | Adverse Event | 1 |
| Study Period IV | Lack of Efficacy | 1 |
| Study Period IV | Lost to Follow-up | 3 |
| Study Period IV | Parent/Caregiver Decision | 1 |
Baseline characteristics
| Characteristic | Duloxetine |
|---|---|
| Age Continuous | 12.5 years STANDARD_DEVIATION 2.9 |
| Body Mass Index (BMI) | 23.7 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 6.4 |
| Race/Ethnicity African | 17 participants |
| Race/Ethnicity Caucasian | 42 participants |
| Race/Ethnicity East Asian | 1 participants |
| Race/Ethnicity Hispanic | 11 participants |
| Race/Ethnicity Native American | 1 participants |
| Region of Enrollment United States | 72 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 37 Participants |
| Tobacco Use No | 70 participants |
| Tobacco Use Not Available | 1 participants |
| Tobacco Use Yes | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 57 / 72 | 21 / 48 |
| serious Total, serious adverse events | 5 / 72 | 0 / 48 |
Outcome results
Primary
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period II/III
The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.
Time frame: Baseline to 18 Weeks
Population: All enrolled patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period II/III | Worsening of Suicidal Ideation | 1 participants |
| Duloxetine | Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period II/III | Completed suicide | 0 participants |
| Duloxetine | Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period II/III | Non-fatal suicide event | 1 participants |
Primary
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period IV
The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.
Time frame: Between 18 and 30 Weeks
Population: Number of enrolled patients with baseline and post-baseline values in Period IV.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period IV | Completed suicide | 0 participants |
| Duloxetine | Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period IV | Non-fatal suicide event | 0 participants |
| Duloxetine | Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period IV | Worsening of Suicidal Ideation | 1 participants |
Primary
Number of Participants Meeting Criteria for Potentially Clinically Significant Electrocardiograms at Any Time in Period II/III
Total number of patients with any abnormal post-baseline values, based on all values at scheduled and unscheduled visits. Criteria: High QRS Interval = ≥100 milliseconds (msec); High QTc Bazette's or Fredericia's correction - Female = ≥470 msec; High QTc Bazette's or Fredericia's correction - Male = ≥450 msec.
Time frame: Baseline to 18 Weeks
Population: Number of patients with baseline (and none abnormal) and post-baseline values, based on all values at scheduled and unscheduled visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Electrocardiograms at Any Time in Period II/III | High QTc Fredericia's Correction (N=65) | 0 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Electrocardiograms at Any Time in Period II/III | High QRS Interval (N=63) | 1 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Electrocardiograms at Any Time in Period II/III | High QTc Bazette's Correction (N=64) | 2 participants |
Primary
Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III
The results shown are for all laboratory analytes where PCS criteria were met, based on criteria used for adult studies. Criteria: High Alanine transaminase (\>165 Units/Liter \[U/L\]); High Creatine Phosphokinase (females: \>507 U/L; males:\>594 U/L); Low Glucose (\<2.498 millimoles/L); Low Hematocrit (females: \<0.32; males \<0.37); Low Hemoglobin (females \<5.896 millimoles/L \[mmol/L\] iron; males \<7.137 mmol/L iron); High Inorganic Phosphorus (\>1.776 millimoles/L); Low Leukocyte Count (\<2.8 X10\^9/L).
Time frame: Baseline to 18 Weeks
Population: Total number of patients with baseline (and none abnormal) and post-baseline values, based on all values at scheduled and unscheduled visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | Low Hematocrit (N=60) | 8 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | Low Hemoglobin (N=67) | 1 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | High Alanine Transaminase (N=69)) | 1 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | High Creatine Phosphokinase (N=69) | 6 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | Low Glucose (N=69) | 1 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | High Inorganic Phosphorus (N=62) | 16 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III | Low Leukocyte Count (N=68) | 1 participants |
Primary
Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period IV
The results shown are for all laboratory analytes where PCS criteria were met, based on criteria used for adult studies. Criteria: High Alkaline Phosphatase (\>420 Units/Liter \[U/L\]); Low Hematocrit (females \<0.32; males \<0.37); High Inorganic Phosphorus (\>1.776 millimoles/L).
Time frame: Between 18 and 30 Weeks
Population: Total number of patients with baseline (and none abnormal) and post-baseline values in Period IV, based on all values at scheduled and unscheduled visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period IV | High Alkaline Phosphatase (N=42) | 1 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period IV | Low Hematocrit (N=39) | 1 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period IV | High Inorganic Phosphorus (N=39) | 3 participants |
Primary
Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period II/III
Total number of patients with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Criteria: High Diastolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Systolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Pulse = increase of at least 25 to a value of at least 110.
Time frame: Baseline to 18 Weeks
Population: Number of patients with baseline (and none abnormal) and post-baseline values, based on all values at scheduled and unscheduled visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period II/III | High Diastolic Blood Pressure | 22 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period II/III | High Systolic Blood Pressure | 25 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period II/III | High Pulse | 2 participants |
Primary
Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period IV
Total number of patients with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Criteria: High Diastolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Systolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Pulse = increase of at least 25 to a value of at least 110.
Time frame: Between 18 and 30 Weeks
Population: Number of patients with baseline (and none abnormal) and post-baseline values, based on all values at scheduled and unscheduled visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period IV | High Diastolic Blood Pressure | 3 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period IV | High Systolic Blood Pressure | 1 participants |
| Duloxetine | Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period IV | High Pulse | 0 participants |
Primary
Number of Participants With Emergence of Suicidal Ideation During Period II/III
Emergence of Any Suicidal Ideation: Item 13 of Children's Depression Rating Scale-Revised (CDRS-R) has possible scores of 1 (no thoughts of suicide) to 7 (contemplation of suicide). Emergence of suicidal ideation was defined as an increase in severity of suicidal ideation for those patients who did not have suicidal ideation at baseline (Week 0).
Time frame: Baseline to 18 weeks
Population: All enrolled patients with data for specified category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Number of Participants With Emergence of Suicidal Ideation During Period II/III | 2 participants |
Primary
Number of Participants With Emergence of Suicidal Ideation During Period IV
Emergence of Any Suicidal Ideation: Item 13 of Children's Depression Rating Scale-Revised (CDRS-R) has possible scores of 1 (no thoughts of suicide) to 7 (contemplation of suicide). Emergence of suicidal ideation was defined as an increase in severity of suicidal ideation for those patients who did not have suicidal ideation at baseline (Week 0).
Time frame: Week 0 and Between 18 and 30 Weeks
Population: All enrolled patients with data for specified category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Number of Participants With Emergence of Suicidal Ideation During Period IV | 0 participants |
Primary
Number of Participants With Potentially Clinically Significant Electrocardiograms at Any Time in Period IV
Total number of patients with any abnormal post-baseline values, based on all values at scheduled and unscheduled visits. Criteria: High QRS Interval = ≥100 milliseconds (msec); High QTc Bazette's or Fredericia's correction - Female = ≥470 msec; High QTc Bazette's or Fredericia's correction - Male = ≥450 msec.
Time frame: Between 18 and 30 Weeks
Population: Number of patients with baseline (and none abnormal) and post-baseline values, based on all values at scheduled and unscheduled visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Potentially Clinically Significant Electrocardiograms at Any Time in Period IV | High QRS Interval (N=39) | 1 participants |
| Duloxetine | Number of Participants With Potentially Clinically Significant Electrocardiograms at Any Time in Period IV | High QTc Bazette's Correction (N=41) | 1 participants |
| Duloxetine | Number of Participants With Potentially Clinically Significant Electrocardiograms at Any Time in Period IV | High QTc Fredericia's Correction (N=41) | 0 participants |
Secondary
Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression. Baseline is the same timepoint (Week 0) for both comparisons, but due to differences in number of patients in both periods (II/III vs IV), the baseline values may be slightly different.
Time frame: Week 0 (Baseline), 18 Weeks, 30 Weeks
Population: 18 Week results are for all enrolled patients with a baseline and at least one non-missing post-baseline value; 30 Week results are for the enrolled patients with a baseline and at least one non-missing post-baseline value in Period IV. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 30 Week Change from Baseline (n=45) | -38.8 units on a scale | Standard Deviation 11.14 |
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 18 Week Baseline (n=72) | 61.69 units on a scale | Standard Deviation 8.98 |
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 18 Week Change from Baseline (n=72) | -32.11 units on a scale | Standard Deviation 12.92 |
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 30 Week Baseline (n=45) | 61.8 units on a scale | Standard Deviation 9.28 |
Secondary
Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S)
Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Baseline is the same timepoint (Week 0) for both comparisons, but due to differences in number of patients in both periods (II/III vs IV), the baseline values may be slightly different.
Time frame: Week 0 (Baseline), 18 Weeks, 30 Weeks
Population: 18 Week results are for all enrolled patients with a baseline and at least one non-missing post-baseline value; 30 Week results are for the enrolled patients with a baseline and at least one non-missing post-baseline value in Period IV. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S) | 18 Week Baseline (n=72) | 4.5 units on a scale | Standard Deviation 0.58 |
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S) | 18 Week Change from Baseline (n=72) | -2.11 units on a scale | Standard Deviation 1.17 |
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S) | 30 Week Baseline (n=45) | 4.5 units on a scale | Standard Deviation 0.59 |
| Duloxetine | Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S) | 30 Week Change from Baseline (n=45) | -2.7 units on a scale | Standard Deviation 1.07 |
Secondary
Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose
Plasma samples were obtained at steady state, and approximately 95% of duloxetine concentrations were within the 24 hour dosing interval.
Time frame: Weeks 2, 4, 6, 8, 10, 14, 18
Population: Number of patients in each duloxetine dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose | 15.2 nanograms per milliliter (ng/mL) | Standard Deviation 12 |
| Duloxetine Dose - 30 mg | Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose | 20.8 nanograms per milliliter (ng/mL) | Standard Deviation 21.2 |
| Duloxetine - 60 mg | Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose | 41.1 nanograms per milliliter (ng/mL) | Standard Deviation 34.7 |
| Duloxetine Dose - 90 mg | Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose | 57.6 nanograms per milliliter (ng/mL) | Standard Deviation 43.2 |
| Duloxetine - 120 mg | Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose | 77.6 nanograms per milliliter (ng/mL) | Standard Deviation 54.6 |
Other Pre-specified
Adverse Events Leading to Discontinuation
A listing of adverse events leading to discontinuation from the study. Abbreviation in data table: ADHD = Attention-Deficit/Hyperactivity Disorder.
Time frame: Week 0 (Baseline) to 30 Weeks
Population: All enrolled patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Adverse Events Leading to Discontinuation | Period IV: Irritability | 1 participants |
| Duloxetine | Adverse Events Leading to Discontinuation | Period II/III: Nausea | 1 participants |
| Duloxetine | Adverse Events Leading to Discontinuation | Period II/III: Worsening of ADHD | 1 participants |
| Duloxetine | Adverse Events Leading to Discontinuation | Period II/III: Rash | 1 participants |